A high-salt diet promotes hypertrophic scarring through TRPC3-mediated mitochondrial Ca2+homeostasis dysfunction

作者全名："Xia, Weijie; Wang, Qianran; Lin, Shaoyang; Wang, Yuanyuan; Zhang, Junbo; Wang, Hailin; Yang, Xia; Hu, Yingru; Liang, Huaping; Lu, Yuangang; Zhu, Zhiming; Liu, Daoyan"

作者地址："[Xia, Weijie; Wang, Yuanyuan; Zhang, Junbo; Wang, Hailin; Lu, Yuangang] Army Med Univ, Daping Hosp, Res Inst Surg, Dept Plast & Cosmet Surg, Chongqing 400042, Peoples R China; [Wang, Qianran; Lin, Shaoyang; Hu, Yingru; Zhu, Zhiming; Liu, Daoyan] Third Mil Med Univ, Dept Hypertens & Endocrinol, Ctr Hypertens & Metab Dis, Daping Hosp,Army Med Univ, Chongqing 400042, Peoples R China; [Yang, Xia; Liang, Huaping; Liu, Daoyan] Third Mil Med Univ, Dept Wound Infect & Drug, State Key Lab Trauma Burn & Combined Injury, Daping Hosp,Army Med Univ, Chongqing 400042, Peoples R China"

通信作者："Liu, DY (通讯作者)，Third Mil Med Univ, Dept Hypertens & Endocrinol, Ctr Hypertens & Metab Dis, Daping Hosp,Army Med Univ, Chongqing 400042, Peoples R China."

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001053669500001

JCR分区：Q1

影响因子：3.4

年份：2023

卷号：9

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：High salt; TRPC3; ROS; Hypertrophic scar

摘要："Diet High in salt content have been associated with cardiovascular disease and chronic inflam-mation. We recently demonstrated that transient receptor potential canonical 3 (TRPC3) channels regulate myofibroblast transdifferentiation in hypertrophic scars. Here, we examined how high salt activation of TRPC3 participates in hypertrophic scarring during wound healing. In vitro, we confirmed that high salt increased the TRPC3 protein expression and the marker of myofibroblast alpha smooth muscle actin (& alpha;-SMA) in wild-type mice (WT) primary cultured dermal fibroblasts but not Trpc3-/- mice. Activation of TRPC3 by high salt elevated cytosolic Ca2+ influx and mitochondrial Ca2+ uptake in dermal fibroblasts in a TRPC3-dependent manner. High salt acti-vation of TRPC3 enhanced mitochondrial respiratory dysfunction and excessive ROS production by inhibiting pyruvate dehydrogenase action, that activated ROS-triggered Ca2+ influx and the Rho kinase/MLC pathway in WT mice but not Trpc3-/- mice. In vivo, a persistent high-salt diet promoted myofibroblast transdifferentiation and collagen deposition in a TRPC3-dependent manner. Therefore, this study demonstrates that high salt enhances myofibroblast trans-differentiation and promotes hypertrophic scar formation through enhanced mitochondrial Ca2+ homeostasis, which activates the ROS-mediated pMLC/pMYPT1 pathway. TRPC3 deficiency an-tagonizes high salt diet-induced hypertrophic scarring. TRPC3 may be a novel target for hyper-trophic scarring during wound healing."

基金机构："National Natural Science Foundation of China [CSTB2022NSCQ-MSX1681]; Natural Science Foundation of Chongqing, China; [82070441]"

基金资助正文："We are grateful to Tingbing Cao, Lijuan Wang and Youying Huang for their technical support. This research was supported by Natural Science Foundation of Chongqing, China (No. CSTB2022NSCQ-MSX1681) and grants from the National Natural Science Foundation of China (No. 82070441) The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE[35] partner repository with the dataset identifier PXD042087.r <B>Declaration of competing interest</B> The authors declare the following financial interests/personal relationships which may be considered as potential competing in-terests: Daoyan Liu reports financial support was provided by National Natural Science Foundation of China. <B>Acknowledgments</B> We are grateful to Tingbing Cao, Lijuan Wang and Youying Huang for their technical support. This research was supported by Natural Science Foundation of Chongqing, China (No. CSTB2022NSCQ-MSX1681) and grants from the National Natural Science Foundation of China (No. 82070441) The mass spectrometry proteomics data have been deposited to the ProteomeXchange Con-sortium via the PRIDE [35] partner repository with the dataset identifier PXD042087."